title: Longitudinal changes in brains of patients with fluent primary progressive aphasia.
abstract: Primary progressive aphasia (PPA) is a rare clinical dementia syndrome with predominant, progressive language impairment. Clinical symptoms, linguistic impairment and the course of the disease may vary considerably between patients. In order to capture these aspects, longitudinal assessments of neurofunctional changes in PPA including their relationship to behaviour and clinical symptoms are mandatory, ideally at intervals shorter than 1 year. Here, we report a longitudinal fMRI study investigating the development of lexical processing and their neural basis in PPA patients over 1year. Four logopenic PPA patients and four matched controls were scanned 3 times (T1, T2, T3, at 6months intervals) while performing a visual lexical decision task on German words and pseudowords. Group differences for the lexicality effect (pseudowords>words) were assessed at time point T1 and its longitudinal changes in the BOLD signal associated with the lexicality effect were analysed. Brain atrophy was assessed with a high-resolution MPRAGE sequence and analysed using deformation based morphometry (DBM). From the very beginning of the study, PPA patients showed reduced left-hemispheric and increased right-hemispheric activations compared to controls. During the progression of the disease, activation increased predominantly in left posterior middle temporal gyrus (pMTG) and inferior frontal junction area, whereas the same regions decreased in activity in control brains. Interestingly, DBM data showed that this increase in activation in PPA patients was accompanied by progressing atrophy in the same regions. At a behavioural level, the accuracy in the lexical decision task was comparably high for both groups during the whole period of examination, despite some large variability between patients. To conclude, the dissociation between (i) maintained high performance, (ii) increased activity in regions involved in lexical access such as pMTG, and (iii) progressive atrophy of the very same regions supports the notion of a compensatory mechanism in brains of PPA patients for maintaining language while brain atrophy is progressing. The activity increase within a left-lateralised fronto-temporal network seems vital for high-level performance, whereas initial right-hemispheric recruitment of homologue language regions, which is reminiscent of that in vascular aphasics, has no continuous impact on lexical performance.
authors.affiliation: Section Structural Functional Brain Mapping, Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical School, RWTH Aachen University, Aachen, Germany; JARA - Translational Brain Medicine, Jülich and Aachen, Germany; Research Centre Jülich, Institute of Neuroscience and Medicine (INM-1, INM-2), Jülich, Germany; Section Neurological Cognition Research, Department of Neurology, Medical School, RWTH Aachen University, Aachen, Germany. Electronic address: sheim@ukaachen.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Heim
authors.affiliation: JARA - Translational Brain Medicine, Jülich and Aachen, Germany; Research Centre Jülich, Institute of Neuroscience and Medicine (INM-1, INM-2), Jülich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Pieperhoff
authors.affiliation: JARA - Translational Brain Medicine, Jülich and Aachen, Germany; Section Neurological Cognition Research, Department of Neurology, Medical School, RWTH Aachen University, Aachen, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Grande
authors.affiliation: JARA - Translational Brain Medicine, Jülich and Aachen, Germany; Research Centre Jülich, Institute of Neuroscience and Medicine (INM-1, INM-2), Jülich, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Kuijsten
authors.affiliation: Section Structural Functional Brain Mapping, Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical School, RWTH Aachen University, Aachen, Germany; JARA - Translational Brain Medicine, Jülich and Aachen, Germany; Research Centre Jülich, Institute of Neuroscience and Medicine (INM-1, INM-2), Jülich, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Wellner
authors.affiliation: Section Structural Functional Brain Mapping, Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical School, RWTH Aachen University, Aachen, Germany; JARA - Translational Brain Medicine, Jülich and Aachen, Germany; Research Centre Jülich, Institute of Neuroscience and Medicine (INM-1, INM-2), Jülich, Germany.
authors.forename: Louise Etcheverry
authors.initials: LE
authors.lastname: Sáez
authors.affiliation: JARA - Translational Brain Medicine, Jülich and Aachen, Germany; Research Centre Jülich, Institute of Neuroscience and Medicine (INM-1, INM-2), Jülich, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schulte
authors.affiliation: Department of Neurology, University Hospital HHU, Düsseldorf, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Südmeyer
authors.affiliation: Research Centre Jülich, Institute of Neuroscience and Medicine (INM-1, INM-2), Jülich, Germany.
authors.forename: Svenja
authors.initials: S
authors.lastname: Caspers
authors.affiliation: JARA - Translational Brain Medicine, Jülich and Aachen, Germany; Research Centre Jülich, Institute of Neuroscience and Medicine (INM-1, INM-2), Jülich, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Minnerop
authors.affiliation: Section Neurological Cognition Research, Department of Neurology, Medical School, RWTH Aachen University, Aachen, Germany.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Binkofski
authors.affiliation: Section Neurological Cognition Research, Department of Neurology, Medical School, RWTH Aachen University, Aachen, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Huber
authors.affiliation: Section Structural Functional Brain Mapping, Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical School, RWTH Aachen University, Aachen, Germany; JARA - Translational Brain Medicine, Jülich and Aachen, Germany; Research Centre Jülich, Institute of Neuroscience and Medicine (INM-1, INM-2), Jülich, Germany; C. and O. Vogt Instutute for Brain Research, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Amunts
mesh_terms: D000368:Aged; D018888:Aphasia, Primary Progressive / Q000473:pathology* / Q000503:physiopathology*; D001284:Atrophy; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D001931:Brain Mapping; D003657:Decision Making; D018450:Disease Progression; D005260:Female; D006801:Humans; D007802:Language; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged
keywords: Atrophy; Compensation; Dementia; FTLD; Language; Lexical access; PPA; Progression; Visual lexical decision; fMRI